Louann Brizendine was a self-described feminist of the '70s, plowing through male-dominated medical school, constantly questioning the patriarchal establishment. So when she was sitting in a class one day and a professor started talking about a science experiment in male rats, Brizendine raised her hand.

At the time, Brizendine said, "I just thought, 'Oh, right, you wouldn't want to mess up your data.' It wasn't until years later that I was horrified."

Decades after Brizendine's classroom experience, not much has changed. Most of the early lab and animal research in medicine is done on males, and with almost no consideration given to the subtle - and not-so-subtle - differences between male and female biology.

True, there have been tremendous advances in studying women's health issues and including women in drug trials and clinical studies. Most of those changes followed a 1993 mandate by the National Institutes of Health that women be included in such studies.

But when it comes to basic science - studying the molecular mechanics of diseases in cells and tissues and in mice and rats - almost all of the work is on subjects with the male XY chromosome pairing.

Stanford, at least, is aiming to dig into that problem with the creation of a new center focused on sex and gender in health. The Stanford Center for Health Research on Women and Sex Differences in Medicine officially opens Wednesday with a conference on sex, gender and the brain, at which Brizendine, now a UCSF psychiatrist who has written two books on the male and female brain, is speaking.

"For just about everything in medical science, we're still very male-focused," said Marcia Stefanick, an obstetrics and gynecology professor at Stanford who is co-director of the new center. "Our basic understanding is missing a key ingredient, and that is the sex difference."

Sex refers to the basic biology of a male or female, primarily to the internal and external organs that separate sexes, plus the chromosomal and hormonal differences. Gender refers to the self-identity of a man or woman - or a boy or girl - based on societal and cultural definitions of masculinity and femininity.

Both sex and gender influence health, but in different ways. Gender is more likely to have environmental or behavioral effects, while sex will have a larger biological impact, usually due to genetic or hormonal influences. Frequently, their impacts are intertwined.

Research lacking

Even as scientists are becoming increasingly aware of differences between men and women when it comes to a variety of health issues - from higher rates of anxiety and dementia in women to a greater likelihood of autism and Parkinson's disease in men - there is a remarkable lack of research being done to get at the underlying reasons for those differences.

"I don't want to paint the picture that one should study both sexes in every study," said Irving Zucker, a UC Berkeley behavioral psychologist who has studied sex and gender bias in scientific research. If certain diseases primarily affect just males or just females, it's probably fine to focus research on that sex.

But in general, "it's imperative to study both sexes," he said. "There's an abundance of evidence that says studying one sex isn't going to necessarily allow you to generalize to the other sex."

Zucker and a colleague published a study in 2010 showing that the majority of basic scientific research was done on males only, and more often than not, scientists didn't even identify which sex they were working with.

Males preferred

In the 10 research fields that Zucker looked at, eight of them showed a strong preference for using male subjects over females - the only two fields where females dominated were immunology and reproduction.Even in diseases from which women were more likely to suffer than men, male subjects still were preferred over females. Women are 2.5 times more likely than men to suffer anxiety disorders, for example, and yet most anxiety studies on animals involved males.

By focusing so much research on males at the exclusion of females, Zucker and other researchers say, scientists may be missing important clues to disease mechanisms or treatments that involve sex biology - whether there are certain genetic traits linked to the X or Y chromosome that make women more or less vulnerable to disease, for example, or what role estrogen plays in disease development.

And they may be causing harm. In the past decade, 8 of the 10 drugs that were pulled from the market for being unsafe were found to have more serious side effects in women than in men, said Stefanick.

Another notable example where ignoring sex has been problematic is in Alzheimer's disease. More than a decade ago, scientists found a single gene mutation that increases risk, but primarily in females. But for years, scientists ignored that finding and studied that mutation in men and women equally, and in primarily male rodents and cell lines.

Scientists kept getting confusing results when they studied the mutation - some studies would show an increased risk from it, others wouldn't - and now many researchers believe that was because the results were muddied by including male and female subjects.

"This gender effect had been completely buried," said Dr. Michael Greicius, a Stanford neuroscientist. "That means all the work that's been done looking at how (the genetic mutation) increases the risk has been substantially diluted by the way we're equating men and women. It raises a bunch of concerns in research and clinical work."

What's already known

In general, scientists are becoming increasingly aware of the role the earliest biological and environmental influences play in the long-term development of disease. What the fetus is exposed to in the womb may alter his or her risk of developing breast cancer or any number of other diseases in adulthood.

Yet little is understood about the long-term effects of the early flush of hormones on fetuses and infants. Males are essentially "marinated" in testosterone in the womb, Brizendine said, and females are similarly flooded with estrogen, although their hormones don't typically kick in until after birth.

That first hormone exposure - responsible for so many traits that ultimately and obviously divide the sexes - likely triggers a whole host of long-term biological processes that may protect some people from disease and make others more vulnerable. The same may be true of the hormonal changes that come with puberty, pregnancy and menopause.

"The male and female brains and the male and female bodies are more alike than different. But it's ridiculous and stupid to say there aren't any differences," Brizendine said. "It's time that we started diving deeper into how sex differences play out in medical diseases."

One irony is that the hormonal influences that account for much of the differences between sexes may also explain why male subjects have dominated medical research for so long. Scientists will frequently say that studying males is easier - they don't have monthly hormonal cycles, for example, and they can't get pregnant.

Yes, Stefanick said, the female of the species is very complex.

More to look at

"In females, to do really good research, we need to look at their (menstrual) phases, we need to compare pre- and post-menopausal states, we need to study pregnant women," she said. "Males are easier."

But she and other scientists said that's a poor reason to omit female subjects. They still make up half of the species, and it's been proved time and again that what's true for males isn't always true for females.

"It seems like something that is so obvious," said Dr. Lynn Westphal, Stefanick's co-director at the new Stanford center. "But I guess it's not as obvious as we think. We've missed a lot of opportunities not doing any research on women. We're really trying to refocus people now."